KEGG   PATHWAY: zab04068
Entry
zab04068                    Pathway                                
Name
FoxO signaling pathway - Zonotrichia albicollis (white-throated sparrow)
Description
The forkhead box O (FOXO) family of transcription factors regulates the expression of genes in cellular physiological events including apoptosis, cell-cycle control, glucose metabolism, oxidative stress resistance, and longevity. A central regulatory mechanism of FOXO proteins is phosphorylation by the serine-threonine kinase Akt/protein kinase B (Akt/PKB), downstream of phosphatidylinositol 3-kinase (PI3K), in response to insulin or several growth factors. Phosphorylation at three conserved residues results in the export of FOXO proteins from the nucleus to the cytoplasm, thereby decreasing expression of FOXO target genes. In contrast, the stress-activated c-Jun N-terminal kinase (JNK) and the energy sensing AMP-activated protein kinase (AMPK), upon oxidative and nutrient stress stimuli phosphorylate and activate FoxOs. Aside from PKB, JNK and AMPK, FOXOs are regulated by multiple players through several post-translational modifications, including phosphorylation, but also acetylation, methylation and ubiquitylation.
Class
Environmental Information Processing; Signal transduction
Pathway map
zab04068  FoxO signaling pathway
zab04068

Other DBs
GO: 0009267
Organism
Zonotrichia albicollis (white-throated sparrow) [GN:zab]
Gene
102066530  TGFB2; transforming growth factor beta-2 [KO:K13376]
102066760  TGFB3; transforming growth factor beta-3 [KO:K13377]
102069625  TGFBR1; TGF-beta receptor type-1 [KO:K04674] [EC:2.7.11.30]
102071453  TGFBR2; TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
102074010  TGF-beta receptor type-2 [KO:K04388] [EC:2.7.11.30]
102062056  SMAD3; mothers against decapentaplegic homolog 3 isoform X1 [KO:K23605]
102072162  STK11; serine/threonine-protein kinase STK11 [KO:K07298] [EC:2.7.11.1]
102067793  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 [KO:K07198] [EC:2.7.11.31]
102063815  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
102075256  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
102067496  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 isoform X1 [KO:K07199]
102074575  5'-AMP-activated protein kinase subunit gamma-1 [KO:K07200]
102062112  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 [KO:K07200]
102067698  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X2 [KO:K07200]
102070076  NLK; serine/threonine-protein kinase NLK isoform X1 [KO:K04468] [EC:2.7.11.24]
102063901  SKP2; S-phase kinase-associated protein 2 [KO:K03875]
102063986  MDM2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
102060643  SETD7; histone-lysine N-methyltransferase SETD7 [KO:K11431] [EC:2.1.1.364]
102069892  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
102067803  CREBBP; CREB-binding protein [KO:K04498] [EC:2.3.1.48]
102064938  SIRT1; NAD-dependent protein deacetylase sirtuin-1 [KO:K11411] [EC:2.3.1.286]
102072130  USP7; ubiquitin carboxyl-terminal hydrolase 7 [KO:K11838] [EC:3.4.19.12]
102060543  MAPK8; mitogen-activated protein kinase 8 isoform X3 [KO:K04440] [EC:2.7.11.24]
102068975  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
102070887  mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
102060816  STK4; serine/threonine-protein kinase 4 isoform X1 [KO:K04411]
102063644  IGF1; insulin-like growth factor I [KO:K05459]
102066292  IGF1R; insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
102072773  INS; insulin [KO:K04526]
102069793  INSR; insulin receptor [KO:K04527] [EC:2.7.10.1]
102067323  IRS1; insulin receptor substrate 1 [KO:K16172]
102068148  IRS2; insulin receptor substrate 2 [KO:K07187]
102061645  IRS4; insulin receptor substrate 4 [KO:K07187]
102064934  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
102075147  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X2 [KO:K00922] [EC:2.7.1.153]
102069576  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102072114  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
102070553  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
102060529  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
102075317  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
102074629  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
102073615  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
102064718  PTEN; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
102070994  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102071413  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102075037  SGK1; serine/threonine-protein kinase Sgk1 isoform X1 [KO:K13302] [EC:2.7.11.1]
102071180  SGK2; serine/threonine-protein kinase Sgk2 isoform X1 [KO:K13303] [EC:2.7.11.1]
102063349  serine/threonine-protein kinase Sgk3 [KO:K13304] [EC:2.7.11.1]
102073742  FOXO1; forkhead box protein O1 [KO:K07201]
102067425  FOXO3; forkhead box protein O3 [KO:K09408]
102070841  GRM1; metabotropic glutamate receptor 1 isoform X1 [KO:K04603]
102068825  HOMER1; homer protein homolog 1 [KO:K15010]
102071997  HOMER2; homer protein homolog 2 isoform X3 [KO:K15010]
102063133  casein kinase I [KO:K08960] [EC:2.7.11.1]
102065743  IL6; interleukin-6 [KO:K05405]
102074567  IL10; interleukin-10 [KO:K05443]
102062617  STAT3; signal transducer and activator of transcription 3 [KO:K04692]
102065155  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
102066957  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
102075088  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
102065734  son of sevenless homolog 2 [KO:K03099]
102064587  SOS1; son of sevenless homolog 1 [KO:K03099]
102070663  HRAS; GTPase HRas [KO:K02833]
102062345  KRAS; GTPase KRas [KO:K07827]
102063862  NRAS; GTPase NRas [KO:K07828]
102072406  BRAF; serine/threonine-protein kinase B-raf [KO:K04365] [EC:2.7.11.1]
102068297  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
102061434  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102064782  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102066965  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102067210  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
102063173  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
102063357  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
102067622  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
106630693  cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
102072574  FOXG1; forkhead box protein G1 [KO:K09385]
102072889  CCNB2; G2/mitotic-specific cyclin-B2 [KO:K21770]
102063435  CCND1; G1/S-specific cyclin-D1 isoform X1 [KO:K04503]
102075450  CCND2; G1/S-specific cyclin-D2 [KO:K10151]
102068359  CCNG2; cyclin-G2 [KO:K10146]
102062317  cyclin-dependent kinase 4 inhibitor B isoform X1 [KO:K04685]
102066391  cyclin-dependent kinase 4 inhibitor B [KO:K04685]
102066168  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
102062405  CDKN1B; cyclin-dependent kinase inhibitor 1B isoform X1 [KO:K06624]
102060989  RBL2; retinoblastoma-like protein 2 [KO:K16332]
102062139  PLK1; serine/threonine-protein kinase PLK1 [KO:K06631] [EC:2.7.11.21]
102065842  PLK2; serine/threonine-protein kinase PLK2 [KO:K08861] [EC:2.7.11.21]
102071391  PLK3; serine/threonine-protein kinase PLK3 [KO:K08862] [EC:2.7.11.21]
102069338  PLK4; serine/threonine-protein kinase PLK4 [KO:K08863] [EC:2.7.11.21]
102066719  GADD45G; growth arrest and DNA damage-inducible protein GADD45 gamma [KO:K04402]
102065064  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
102075177  BCL2L11; bcl-2-like protein 11 [KO:K16341]
102067007  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
102073230  BCL6; B-cell lymphoma 6 protein [KO:K15618]
106629461  ATG12; ubiquitin-like protein ATG12 [KO:K08336]
102067098  GABARAPL2; gamma-aminobutyric acid receptor-associated protein-like 2 [KO:K08341]
102069837  GABARAPL1; gamma-aminobutyric acid receptor-associated protein-like 1 [KO:K08341]
102066385  CAT; catalase [KO:K03781] [EC:1.11.1.6]
102063073  SOD2; superoxide dismutase [Mn], mitochondrial isoform X1 [KO:K04564] [EC:1.15.1.1]
102062101  ATM; serine-protein kinase ATM isoform X1 [KO:K04728] [EC:2.7.11.1]
102063732  PCK1; phosphoenolpyruvate carboxykinase, cytosolic [GTP] isoform X1 [KO:K01596] [EC:4.1.1.32]
102063362  G6PC2; glucose-6-phosphatase 2 isoform X1 [KO:K01084] [EC:3.1.3.9]
102064265  G6PC; glucose-6-phosphatase isoform X1 [KO:K01084] [EC:3.1.3.9]
102063338  KLF2; Krueppel-like factor 2 [KO:K17845]
102066416  S1PR1; sphingosine 1-phosphate receptor 1 [KO:K04288]
102071733  S1PR4; sphingosine 1-phosphate receptor 4 [KO:K04293]
102065378  RAG1; V(D)J recombination-activating protein 1 [KO:K10628] [EC:2.3.2.27]
102065190  RAG2; V(D)J recombination-activating protein 2 [KO:K10988]
102065412  FBXO25; F-box only protein 25 isoform X1 [KO:K10305]
102067889  FBXO32; F-box only protein 32 [KO:K10305]
Compound
C00008  ADP
C00020  AMP
C00025  L-Glutamate
C00031  D-Glucose
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
  Authors
Glauser DA, Schlegel W
  Title
The emerging role of FOXO transcription factors in pancreatic beta cells.
  Journal
J Endocrinol 193:195-207 (2007)
DOI:10.1677/JOE-06-0191
Reference
  Authors
van der Horst A, Burgering BM
  Title
Stressing the role of FoxO proteins in lifespan and disease.
  Journal
Nat Rev Mol Cell Biol 8:440-50 (2007)
DOI:10.1038/nrm2190
Reference
  Authors
Zhang X, Tang N, Hadden TJ, Rishi AK
  Title
Akt, FoxO and regulation of apoptosis.
  Journal
Biochim Biophys Acta 1813:1978-86 (2011)
DOI:10.1016/j.bbamcr.2011.03.010
Reference
  Authors
Eijkelenboom A, Burgering BM
  Title
FOXOs: signalling integrators for homeostasis maintenance.
  Journal
Nat Rev Mol Cell Biol 14:83-97 (2013)
DOI:10.1038/nrm3507
Reference
  Authors
Daitoku H, Fukamizu A
  Title
FOXO transcription factors in the regulatory networks of longevity.
  Journal
J Biochem 141:769-74 (2007)
DOI:10.1093/jb/mvm104
Reference
  Authors
Hedrick SM
  Title
The cunning little vixen: Foxo and the cycle of life and death.
  Journal
Nat Immunol 10:1057-63 (2009)
DOI:10.1038/ni.1784
Reference
  Authors
Coffer PJ, Burgering BM
  Title
Forkhead-box transcription factors and their role in the immune system.
  Journal
Nat Rev Immunol 4:889-99 (2004)
DOI:10.1038/nri1488
Reference
  Authors
Ro SH, Liu D, Yeo H, Paik JH
  Title
FoxOs in neural stem cell fate decision.
  Journal
Arch Biochem Biophys 534:55-63 (2013)
DOI:10.1016/j.abb.2012.07.017
Reference
  Authors
Maiese K, Chong ZZ, Shang YC
  Title
OutFOXOing disease and disability: the therapeutic potential of targeting FoxO proteins.
  Journal
Trends Mol Med 14:219-27 (2008)
DOI:10.1016/j.molmed.2008.03.002
Reference
  Authors
Hagenbuchner J, Ausserlechner MJ
  Title
Mitochondria and FOXO3: breath or die.
  Journal
Front Physiol 4:147 (2013)
DOI:10.3389/fphys.2013.00147
Reference
  Authors
Maiese K, Chong ZZ, Shang YC
  Title
"Sly as a FOXO": new paths with Forkhead signaling in the brain.
  Journal
Curr Neurovasc Res 4:295-302 (2007)
DOI:10.2174/156720207782446306
Reference
  Authors
Oh HM, Yu CR, Dambuza I, Marrero B, Egwuagu CE
  Title
STAT3 protein interacts with Class O Forkhead transcription factors in the cytoplasm and regulates nuclear/cytoplasmic localization of FoxO1 and FoxO3a proteins in CD4(+) T cells.
  Journal
J Biol Chem 287:30436-43 (2012)
DOI:10.1074/jbc.M112.359661
Reference
  Authors
Huang H, Tindall DJ
  Title
Regulation of FOXO protein stability via ubiquitination and proteasome degradation.
  Journal
Biochim Biophys Acta 1813:1961-4 (2011)
DOI:10.1016/j.bbamcr.2011.01.007
Reference
  Authors
Greer EL, Brunet A
  Title
FOXO transcription factors at the interface between longevity and tumor suppression.
  Journal
Oncogene 24:7410-25 (2005)
DOI:10.1038/sj.onc.1209086
Reference
  Authors
Seoane J, Le HV, Shen L, Anderson SA, Massague J
  Title
Integration of Smad and forkhead pathways in the control of neuroepithelial and glioblastoma cell proliferation.
  Journal
Cell 117:211-23 (2004)
DOI:10.1016/S0092-8674(04)00298-3
Reference
  Authors
Yamagata K, Daitoku H, Takahashi Y, Namiki K, Hisatake K, Kako K, Mukai H, Kasuya Y, Fukamizu A
  Title
Arginine methylation of FOXO transcription factors inhibits their phosphorylation by Akt.
  Journal
Mol Cell 32:221-31 (2008)
DOI:10.1016/j.molcel.2008.09.013
Reference
  Authors
van der Horst A, de Vries-Smits AM, Brenkman AB, van Triest MH, van den Broek N, Colland F, Maurice MM, Burgering BM
  Title
FOXO4 transcriptional activity is regulated by monoubiquitination and USP7/HAUSP.
  Journal
Nat Cell Biol 8:1064-73 (2006)
DOI:10.1038/ncb1469
Reference
  Authors
Zhang Y, Gan B, Liu D, Paik JH
  Title
FoxO family members in cancer.
  Journal
Cancer Biol Ther 12:253-9 (2011)
DOI:10.4161/cbt.12.4.15954
Reference
  Authors
Van Der Heide LP, Hoekman MF, Smidt MP
  Title
The ins and outs of FoxO shuttling: mechanisms of FoxO translocation and transcriptional regulation.
  Journal
Biochem J 380:297-309 (2004)
DOI:10.1042/BJ20040167
Related
pathway
zab00010  Glycolysis / Gluconeogenesis
zab00020  Citrate cycle (TCA cycle)
zab00190  Oxidative phosphorylation
zab04010  MAPK signaling pathway
zab04110  Cell cycle
zab04120  Ubiquitin mediated proteolysis
zab04140  Autophagy - animal
zab04210  Apoptosis
zab04350  TGF-beta signaling pathway
zab04910  Insulin signaling pathway
KO pathway
ko04068   
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